Bioequivalence: Some relevant clinical and biopharmaceutic aspects

Evaluation of bioequivalence is mandatory in order to establish interchangeability of generic drugs. Although there are several factors that may influence the bioavailability of drugs after oral administration, special attention has received solubility and permeability. In fact, drugs have been classified in four groups depending on them. In general, it has been established that biowaiver can be given to BCS class I drugs (high permeability, high solubility) since absorption of this kind of drugs is not importantly affected. There is controversy about class III drugs (high solubility, low permeability), since FDA does not give biowaiver, whereas, WHO establish that biowaiver may be given. Class II and IV require bioequivalence studies. In order to contribute to a harmonization, several examples for different kind of drugs, in which dissolution profile and comparative bioavailability were evaluated, are presented in this chapter. In general, for oral administered drugs, bioequivalence allows us to warrant that interchangeability is possible. However, in the case of drugs that are intended for site effect administration, such as inhaled suspensions, measurement of plasma levels does not warrant the therapeutic equivalence. In such cases, measurement of the effect is a good approach to demonstrate the interchangeability. Results about studies carried out with this kind of drugs are given and the clinical relevance of this kind of studies is provided. All data provided in this chapter allow us to conclude that research focused to improve regulation in bioequivalence will contribute to a better quality of generic drugs.